1. 1
   The first 15 bases of the coding strand of a gene read ATG GGA CTT TGG AAA, which codes for methionine–glycine–leucine–tryptophan–lysine. Three variant alleles of the gene are found in a population. In allele X the sixth base, A, is replaced by G, so the codon GGA becomes GGG, which also codes for glycine. In allele Y the twelfth base, G, is replaced by A, so the codon TGG becomes TGA, which is a stop codon. In allele Z one extra base, C, is inserted between the third and fourth bases. The full gene codes for a polypeptide of 310 amino acids.

   (a)

   Which statement describes allele X?

   [1 mark]

   • AIt is an insertion that causes a frameshift
   • BIt is a base substitution that replaces glycine with a different amino acid
   • CIt is a base substitution that does not change the amino acid sequence of the polypeptide
   • DIt is a deletion that removes glycine from the polypeptide

   (b)

   What is the most likely consequence of allele Z?

   [1 mark]

   • AOnly the second amino acid of the polypeptide is changed
   • BEvery codon after the insertion is read in a different frame, so the amino acid sequence is altered from the second amino acid onwards
   • CThe polypeptide is unchanged because the genetic code is degenerate
   • DThe polypeptide is one amino acid longer but otherwise unchanged

   (c)

   Explain why allele Y is likely to produce a non-functional polypeptide even though it is a single base substitution.

   [2 marks]

   Total for question 1: 4 marks

2. 2
   Researchers grew identical cultures of baker's yeast (Saccharomyces cerevisiae) and measured how often cells gained a mutation that inactivates a gene called CAN1; only cells with an inactive CAN1 gene can grow on plates containing a toxic drug. Untreated cultures gave 2 mutants per 10⁷ cells. Cultures exposed to ultraviolet light for 30 seconds gave 40 mutants per 10⁷ cells. Cultures treated with ethyl methanesulfonate (EMS), a chemical that attaches ethyl groups to guanine, gave 120 mutants per 10⁷ cells. When the CAN1 gene of 50 EMS-induced mutants was sequenced, the mutations were found at many different positions spread along the gene, but 46 of the 50 were substitutions in which a G was replaced by an A.

   (a)

   What is the most likely cause of the CAN1 mutants in the untreated cultures?

   [1 mark]

   • AErrors made during DNA replication or repair
   • BThe yeast cells changing the CAN1 gene deliberately so that they could survive the drug
   • CCrossing over between homologous chromosomes creating new base sequences
   • DEthyl groups added to guanine by EMS in the growth medium

   (b)

   Which conclusion is best supported by the sequencing results?

   [1 mark]

   • AEMS changes only one specific base in the CAN1 gene
   • BEvery base in the CAN1 gene is equally likely to be mutated by EMS
   • CThe mutations occurred in CAN1 because the cells needed resistance to the drug
   • DEMS-induced mutations can occur at many positions, but some bases are more likely to mutate than others

   (c)

   Calculate how many times more frequent CAN1 mutants were after EMS treatment than in untreated cultures, and suggest why the true number of mutations caused by EMS in the gene is likely to be higher than the number detected.

   [2 marks]

   Total for question 2: 4 marks

3. 3
   A 35-year-old woman buys a direct-to-consumer genetic test online. The report states that she carries a variant of the BRCA1 gene that, in population studies, is associated with a 60% lifetime risk of breast cancer, compared with about 12% in the general population. She later learns that her father also carries the variant. Her brother, who had frequent sunburn as a teenager, has had a melanoma (a skin cancer) removed. The melanoma cells carry a mutation in a gene called BRAF that is not present in DNA extracted from his blood cells.

   (a)

   Explain why the woman's BRCA1 variant could be passed on to her children but the BRAF mutation in her brother's melanoma could not be passed on to his children.

   [3 marks]

   (b)

   Discuss the benefits and risks of the woman receiving this information from a commercial genetic test without expert interpretation.

   [4 marks]

   Total for question 3: 7 marks

4. 4
   In most mammals, production of the enzyme lactase, which digests the milk sugar lactose, falls sharply after weaning. In some human populations, adults continue to produce lactase (lactase persistence). In Europeans this is mainly due to a single base substitution (C replaced by T) in a regulatory region of DNA close to the lactase gene. The T allele has a frequency of about 0.7 in parts of northern Europe, where cattle have been kept for milk for several thousand years, but below 0.05 in many East Asian populations. Ancient DNA shows that the T allele was rare in Europe about 7000 years ago.

   (a)

   Explain how the lactase persistence allele could have arisen and then increased in frequency in dairy-farming populations.

   [6 marks]

   (b)

   Discuss the view that gene mutations are harmful to living organisms.

   [6 marks]

   Total for question 4: 12 marks

End of questions